Good day, ladies and gentlemen and welcome to the Prothena Fourth Quarter 2014 Financial Results Conference Call. At this time, all participants are in a listen only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] As a reminder, today's conference is being recorded. I would now like to turn the conference over to Tran Nguyen, CFO of Prothena. Sir, you may begin.

Thank you, Candice. Good afternoon everyone and welcome to Prothena's conference call to review our fourth quarter and full year 2014 financial results, 2015 financial guidance and business progress. Please review the press release we issued earlier today which is available at our Web site at Prothena.com and is also attached to our Form 8-K filed today's with the SEC. On today's call are Dr. Dale Schenk, our President and Chief Executive Officer who will discuss our 2014 highlights and corporate accomplishments. Dr. Gene Kinney, our Chief Scientific Officer and Head of research and development, who will review our pipeline development, and I will provide financial results for the fourth quarter and full year of 2014 and comment on the our 2015 financial guidance. Finally, Dale will provide you with our upcoming milestones and then he will open the call up for Q&A. Before we begin, I would like to remind you during the course of today's call we will be making statements regarding Prothena's future expectations, plans and prospects that constitute forward-looking statements under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are based on estimates, projections and assumptions that may prove not to be accurate and actual results may differ materially from those anticipated due to known and unknown risks, uncertainties and other factors. For a discussion of the risks associated with our forward-looking statements please see our press release issued today as well as our most recent Form 10-K and 10-Q filed with the SEC and also the Form 10-K we will be soon filing with the SEC. We disclaim any obligation to update our forward-looking statements With that, I would like to turn the call over to Dale.

Thank you, Tran, and thank you all for joining us this afternoon. 2014 was a transformational year for Prothena as we initiated a late stage clinical study, made significant progress with our three lead programs hired and promoted key personnel and strengthened our balance sheet. As you know, Prothena is developing three novel protein immunotherapies for the potential treatment of diseases that involve amyloid or cell adhesion with patient always at the forefront of our efforts. The first two programs target the amyloid proteins implicated in several diseases including AL amyloidosis through NEOD001 and Parkinson's disease through PRX002 and our third program PRX003 targets the cellular traffic involved in psoriasis and other inflammatory diseases. At this time I would like to review our 2014 highlights. Our most advanced program NEOD001 is a monoclonal antibody for the potential treatment of an orphan disease called AL amyloidosis. A grievous, systemic and progressive disease that affects multiple organs and tissues within the body such as heart and kidneys. While there are three main forms of systemic amyloidosis, AL, AA and TTR amyloidosis, patients with AA amyloidosis represent the vast majority of systemic amyloidosis. In December, we announced the initiation of the VITAL Amyloidosis Study, a global Phase 3 registrational trial for NEOD001. This Phase 3 programs was supported and informed by positive data in our Phase 1-2 study and incorporates feedback from U.S. and EU regulators as well as input from KOLs, clinical advisors and patient advocacy groups. Importantly, we were able to move into a Phase 3 study in less than two years after our initial IND filling, a great achievement by any standard. The VITAL Amyloidosis Study is designed to evaluate the effect of NEOD001 when we combine it with standard of care therapy versus standard of care alone. We believe…

Thanks, Dale. I would like to take a moment to echo deals comments that we accomplished several significant milestones in 2014 laying an exciting foundation for progress in 2015 and beyond. Beginning with NEOD001. In December, we reported positive results from our ongoing Phase 1/2 trial where we demonstrated that NEOD001 treated patients showed favorable and renal response rate in comparison to historical data of newly diagnosed patients treated solely with standard of care. As of September 30, 2014, NEOD001 met both the primary and secondary endpoints of the Phase 1/2 study and was shown to be safe and well tolerated for patients with AL amyloidosis. There were no drug-related serious adverse events, no discontinuations due to NEOD001 related adverse events, and no dose limiting toxicities observed. Looking specifically at changes in indicators of organ function, patients treated with single agent NEOD001 showed substantial cardiac and renal responses. 50% or seven of 14 cardiac evaluable patients treated with NEOD001 demonstrated a cardiac response as measured by NT-proBNP levels decreasing by more than 30% and 300 picograms/milliliter. And cardiac responders showed more NT-proBNP decline with added monthly NEOD001 infusion. This compares favorably to an expected 26.5% response rate from historical data for newly diagnosed patients treated solely with standard of care agents that are not approved specifically for AL amyloidosis. It is important to note that increasing levels of NT-proBNP predict higher mortality rates in patients with AL amyloidosis. Conversely, decreasing NT-proBNP predicts lower mortality. Thus, we believe that the clinically meaningful decreases in NT-proBNP demonstrated following NEOD001 treatment in this Phase 1/2 study directly inform our selection of a survival based endpoint for our Phase 3 VITAL study. In addition to the cardiac responses, we demonstrated a clinically relevant response in a second organ. Approximately 43% or six of 14…

Thanks, Gene. First our cash earned from operating activities in 2014 was approximately $1 million compared to guidance of $7 million to $12 million that includes a total of $45 million in upfront and clinical milestone payments through our collaboration with Roche for PRX002 in 2014. As you know these figures do not include the 117.4 million in net proceeds raised through our equity offering in 2014. The favorability of our actual results compared to guidance was driven primarily by lower than anticipated development expenses and to a lesser extent higher-than-expected accrued liabilities. We reported net losses of $13.1 million and $7.2 million for the fourth quarter and full year of 2014 respectively, as compared to net losses of $11.1 million and $41 million for the fourth quarter and full year of 2013 respectively. Net losses per share were $0.48 and $0.29 for the fourth quarter and full year of 2014 respectively, as compared to net losses per share of $.52 and $2.20 for the fourth quarter and full-year of 2013 respectively. Net loss for the fourth quarter and full year of 2014 included share-based compensation expense of $1.4 million and $5.6 million respectively, compared to $1.1 million and $3.1 million for the respective prior period. We reported total revenue of $2 million and $50.9 million for the fourth quarter and full year of 2014 respectively as compared to total revenue of $0.2 million and $0.7 million for the fourth quarter and full year of 2013 respectively. The increase was primarily due to $1.9 million and $50.3 million in collaboration revenue recognized in relation to the PRX002 collaboration with Roche in the fourth quarter and full year of 2014. R&D expenses totaled $10.1 million and $38.5 million for the fourth quarter and full-year of 2014 as compared to $5.6 million…

Thank you, Tran. Looking ahead, we intend to report new data from the expansion phase portion of our NEOD001 Phase 1/2 trial at a medical conference later this year and annually moving forward. We expect data from our single ascending dose trial of PRX002 later this month in March as well as data from the multiple ascending dose trial on the first half of 2016. Finally we expect to initiate the Phase I single ascending dose trial for a third of program, PRX003 in the first half of 2015 and the multiple ascending dose study in 2016. They potentially provide rapid proof of biology in Phase I. At this time I would like to open the call for questions. Operator, please.

[Operator Instructions] Our first question comes from the line of Michael Yee of RBC Capital Markets. Your line is now open.

This is John on behalf of Michael Yee. For PRX002, could you just help us put into context the data we will see this month. I understand it's Phase 1 in healthy, so primarily aim is safety and PK but with biomarker measures such as [knock down] [ph] and alpha-synuclein in the periphery, just curious how much knock down in your view is clinically meaningful. And just bigger picture, Gene briefly laid out why you guys are excited with this approach but how validated is the alpha-synuclein hypothesis in Parkinson's? Is it any different from amyloid beta hypothesis in Alzheimer's and has other drugs shown knock down of alpha-synuclein. Thanks.

Yes. So thanks John for the question. This is Gene. So let me start with just the Phase 1 single ascending dose data. So obviously this is a single ascending dose study, it's a single infusion of PRX002 in population of healthy volunteer subject. Obviously the primary outcome measure as you actively point out is going to be safety and tolerability. Obviously we will also be very interested in the pharmacokinetics of the molecule. We are capturing some biomarkers in this study. It's somewhat limited in terms of what we can look at because it is a non-disease population. But I think one thing we can look at and are eager to look at is how the antibody PRX002 is actually engaging with the target in vivo and what kind of modulation they are. I mean I think a key question obviously in the field, and we can talk about the validation of alpha-synuclein as a target in a second here. But as you go after alpha-synuclein, obviously the first thing you want to know is that you can do so in a safe and well-tolerated manner at doses that actually modulate the peptide in the protein. So that’s an important learning there I think we can get out of this single-dose study. In terms of the validation of alpha-synuclein, maybe I can just say a few words and then Dale may want to chime in here because he has done a lot of [indiscernible] work. But certainly we think there is both good genetic as well as pathologic evidence suggesting that alpha-synuclein is a significant players in both the onset and progression of Parkinson's disease and related synucleinopathy. Certainly there is genetic evidence suggesting duplication, triplication or mutation of alpha-synuclein will, or I should say the genes that [indiscernible] alpha-synuclein will need to early onset Parkinson's disease. We also know that in idiopathic cases of Parkinson's disease this pathology is really almost defined by alpha-synuclein pathology and inclusion. And so we think there is actually very substantial genetic evidence as well as pathological evidence. But maybe, Dale, you can comment further on that.

Yes. You mentioned -- now we have a siren's background, sorry about that. You had the amyloid -- I think the story with Parkinson's and synuclein is actually simpler. There is no debate about which protein in Parkinson's everybody seems to be converging on. Synuclein also -- synuclein is in the neuron as opposed to outside of the neuron, thereby causing damage directly to the neuron itself. And finally, one thing that is easier to tackle in Parkinson's and in Alzheimer's is there is a very peripheral component, clear peripheral component, a clear peripheral component in Parkinson's disease with synuclein and synuclein [indiscernible] that can be interrogated and investigated. So I want to echo the stuff that Gene just said about the genetics and other [technologies] [ph], pretty clarified.

Great. But just following up on that point. So has there been other drugs that have shown knock down in alpha-synuclein whether it's in the brain or the periphery. And then just following up more on that point. So at what point would we know or would you know that the alpha-synuclein hypothesis is no longer a hypothesis and real. Just wondering if, are we going to have to wait years and hundreds of millions of dollars after Phase 3 to finally know, like Alzheimer's disease or is there a stage in Phase 2 or another function endpoints that may give you clear signal. Thanks.

Yes. To me, first to address the first part of your question about knock-down of alpha-synuclein. I mean certainly we can speak to the non-clinical data, right. Where I think there are multiple models of alpha-synuclein over expressing transgenic mice for example, where you see high levels of alpha-synuclein expressed chronically. You see pathology in the brains of those animals and ultimately dysfunction in those animals that is related to that alpha-synuclein pathology. And certainly, and we have published a lot of this work notably with [indiscernible] UCFD. And in that work I think it's pretty clear that these antibodies that we use, particularly those that target alpha-synuclein in the right place and there are wrong places to target alpha-synuclein, that they have very good impact in terms of reducing the pathology but also preserving against those functional deficits. And so I think there is good evidence certainly from the non-clinical data. I don’t know Dale if you want to mention maybe some of the clinical work.

Yes. I mean there is not too much on the clinical side for passive immunotherapy where we are trailblazers. Which is the place we would like to be. And so we will have to wait and see. But to answer your question about the process. Again, every disease is different and I will echo what I said earlier, that Parkinson's as a peripheral component that can be investigated much more easily. No such thing exists in Alzheimer's disease. So Parkinson's, we are going to have to most likely have pretty clear cut biomarker data. And I mean that when I say we feel [gen 02] [ph] have built long before -- sorry, as a stepping into the other movement in point. So the product test will be simpler and more directed and more measurable.

Thank you. And our next question comes from the line of Jason Kantor of Credit Suisse. Your line is now open.

I will put it pretty straight forward, but just as you think about rolling out additional data from the AL amyloidosis study, is there a specific conference that you are going to target annually. Should we think about ASH or is this something that’s going to vary from year to year or is this something that can be fairly predictable?

Yes, I mean Jason -- I think there are the usual suspects in terms of conferences, particularly around hematology you are talking about. Obviously, ASH, [EAJ] [ph], ASCO and there is probably some others as well you can think about. As a rule we are not going to -- we wouldn’t say exactly which conference is because obviously there is this submission process and acceptance of the abstract process that needs to take place for each of these conferences. And on a case by case basis, as we knew we were going to present, we would actually put out a note ahead of time to make sure that anyone that was interested in coming to the conference and taking a look at the data had an opportunity to do that. But it would be premature to actually specifically name a single conference because it would be ahead of the process of submission and acceptance.

And this symposium that you are hosting or participating in, I mean what the expectation for what could come out of that. Is that going to be a place where new clinical data is going to be released or talked about or this is just highlighting the mechanism of action and unmet need and such.

So the intent of the symposium at ADPD, which is being jointly sponsored by ourselves and Roche, is really to focus on the role of alpha-synuclein in Parkinson's disease as well as other synucleinopathies. Really from a molecular basis all the way through to kind of a therapeutic intervention basis. And so that’s the primary focus.

Thank you. And our next question comes from the line of Chris Marai of Oppenheimer. Your line is now open.

Just really quick on VITAL. I was wondering how you think perhaps the current standard of care might impact immune response and therefore potentially impact your treatment in combination. And I guess with respect to that, in your view, how much of your benefit do you think is due to sort of ADCC or other immune sort of mediated aspects versus say structural factors or just antibody binding resulting in structural changes that allow for [plaque] [ph] to dissolve or become dislodged. Thanks.

Thanks, Chris for the question. So let me just start a little bit with the mechanism of action of D1. I mean as I think we have talked about pretty extensively in the past, we believe that there are two kind of aggregated species of [life] [ph] chain that have been implicated in the disease or at least with respect to toxicity in the disease. The soluble aggregated forms and then the insoluble aggregated forms. Soluble aggregated forms are probably a little bit more of a labile form if you will, a bit easier to disrupt and neutralize the toxicity after interaction with an antibody. But as you point out, kind of as a general statement in the field of amyloids, there is some interesting literature suggesting that if you have the insoluble forms of the so called [fibros] [ph] or amyloid itself. Really that’s a poor substrate for macrophage phagocytosis opsonization. But what can happen is after you actually engage that material with an antibody through mediation or through interaction with Fc-gamma receptors, you tend to switch those macrophage into a phenotype which is dominated by phagocytosis. And so we think that that’s certainly a relevant mechanism of action with respect to removal of amyloid from tissue. Chemotherapeutic agents that are standard of care certainly impact the immune system in a general way. I think our read of the data around phagocytosis specifically, the macrophage function is that it's a little bit more mixed in terms of what you might expect there. And so our general feeling is that we think NEOD001 as a standalone agent in the Phase 1/2 program has demonstrated I think very nice effect by our evaluation of the data in a 'organ refractory patient population'. And we think that by combining that with any benefit of a very complementary biology, i.e. turning down the production of new life chain from those plasma clones, that we should see a very complementary effect which should be additive or even synergistic in nature and that comparing that obviously to the standard of care alone. So we are not overly concerned by that but what we do think it's certainly an important mechanism.

Okay. Great. And just with respect to PRX003, the psoriasis trials. Maybe remind us how many patients you have had and when do we expect the data. I am sorry if I missed it. Thanks.

Yes. So we haven't talked about the design of that study yet but I think we have said that we expect the first study to be a single ascending dose study in healthy volunteers and so that’s a pretty straight forward design and approach.

And we have also said that we would initiate the sequential [MED] [ph] in 2016, so that will give you a sense of when that status would read out. And they are of course the primary -- with quality, safety and tolerability, PK immunogenicity from a secondary perspective. We will be looking at exploratory in terms of pharmacodynamic properties too.

Yes, absolutely.

Okay. And then would you be looking at these all in healthy volunteers or would you be looking at within any patients with psoriasis. Thanks.

So we anticipate that we would look at pharmacodynamic effects in both healthy volunteers as well as in the multiple dose study in patients.

Thank you. And our next question comes from the line of Heather Behanna of Wedbush. Your line is now open.

Just a follow up on 003. If you could just talk a little bit about the IL-17 antibodies in psoriasis and sort of what your expectation might be or what you are thinking of going in with 003 considering its mechanism in comparison.

Yes. Thanks, Heather. Great question. So obviously we are encouraged by the anti IL-17 data, particularly in psoriasis. I think it really indicates that IL-17 is playing a very important role in the disease. Where we are differentiated I think in terms of approach is that we are really going after the TH 17 cells themselves, right. So the signature cytokine of the TH 17 cells is certainly IL-17 but that is not the only cytokine that is released by those cells. I point to IL-22 as another example. And so the point being that these TH 17 cells release multiple cytokines which likely stimulate multiple pro-inflammatory pathways. And so it's no surprise then that there are a number of inflammatory disorders where perhaps if the contribution of IL-17 and some of these other cytokines may be differentially important. You could expect to have a broader impact. And so we are quite excited by the opportunity space there. But at the same time in a strategic manner we think that moving forward with psoriasis in the first instance, given the visible nature of the actual disease and the ability to see proof of biology relative quickly, provides an opportunity not only to provide benefit potentially to psoriasis patients, maybe in a way that's differentiated from IL-17 but also allows us strategically to de-risk the program in the molecule in a relatively expeditious way. And then on the back end of that, assuming that the drug is safe, well tolerated and shows the expected proof of biology, we would really open up the opportunity space to additional areas of inflammation beyond that which may or may not be served well by the anti-IL-17 approaches.

I would just add, you might expect differences in pharmacodynamics because in one case you are getting rid of a cytokine and in the second case you are getting rid of the source.

Thank you. [Operator Instructions] And our next question comes from the line of Bert Hazlett of Ladenburg. Your line is now open.

A lots been asked and answered but just following up on the 003 question. So is it fair to summarize that once you get to the proof of principle or at least the demonstration of biologic activity in the psoriasis model, that psoriasis will likely not be the primary indication that’s sought. Or is that too strong a statement.

Yes. Bert, I think that’s too strong a statement. I mean what we would look to do in a positive scenario is first compare the activity with expectations. I think obviously there has to be added benefit to patients with psoriasis to move forward. You are going to want to do that, certainly analysis. But we are not excluding the possibility that there maybe added or differential benefit over and above the anti IL-17. That said, I think probably bigger impact is, you would start to ask the question of what else in addition to psoriasis you could start to think about. And again maybe in a manner that’s differentiated, maybe in areas where the anti IL-17 haven't shown as a robust ever response as has been seen in the psoriasis study.

And I think you have to be very thoughtful and strategic in the general inflammatory disease space. We have been through this before with Tysabri in the sense that we will take all the data that we have. As Gene said, we will look carefully at psoriasis but we will also look at both potential orphan and very very broad indications, large indications as well. Just try and position PRX003 going forward. So a very interesting antibody.

Thank you for that. And then just shifting back to 001 in the VITAL study. The 18 to 30 month seems like, given the urgency that’s necessitated with the condition that it seems like a -- maybe that’s a long time for enrollment. Could you just speak to that and talk about maybe some of the concerns that you might have or the benefits that you might have to be able to swing enrollment either towards the 18 months or for the 30 month.

Absolutely Bert. We are trying to swing enrollment. We are not going to swing it to the 30-month [indiscernible]. All that said, it's a very important question and I think you know it's a pretty wide range and we recognize that. The challenge is obviously, is pretty obvious here. This is an orphan disease for which there is no real precedence for this type of study. So we have done our best estimating. We have certainly looked at trials into other orphan disease spaces, not excluding obviously other systemic amyloidosis. We have also done all the proper homework that you are supposed to do in terms of site surveys and what have you. Talked to a number of KOLs. And so these are our best estimates today. I think it's probably fear to say that as we continue to gain experience in this space, we certainly desire to tighten up this guidance. I wouldn’t expect that until, at the earliest later this year, but potentially into next year as well. But our hope certainly is to -- with real experience under our belt to be able to kind of move this guidance to a closer number in the future.

Thank you for that. Is there a particular geography that you feel more strongly about that you are pushing things toward or is it really more global in nature.

Yes. Now this is a global trial. I mean I think we said back in December 2nd when we talked about this that we were anticipating opening, somewhere around 50 to 60 sites primarily in North America and Europe is where we are focused in the first instance.

Thank you. And I am showing no further questions at this time. I would like to turn the conference back over to Dr. Dale Schenk for any closing remarks.

Okay. Well. Thank you everyone and in conclusion, I would like to reiterate our enthusiasm for this important time in Prothena's evolution. We believe the year ahead will be filled with many important events to progress our programs forward. And thank you for your continued support. Thanks, everyone.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program and you may all disconnect. Have a great day everyone.